52 results about "Aging-associated diseases" patented technology

The ageing of the population is a key issue in the modern societies. The inventors have therefore searched how to determine parameters linked with the biological age of the subject. This has led them to find that characterizing mitochondria in an area of the subject enables to deduce such parameters. For this, the inventors has developed a tool providing with characterizing parameters of a mitochondrion, and notably a morphology parameter of the mitochondrion and an ultrastructure parameter of the mitochondrion. This opens the way of exploiting the characterizing parameters of mitochondria for multiples applications, such as therapy, medicine screening or clinical follow-up for aging related disorders or mitochondrial disorders.

The invention discloses a ternary fusion polypeptide Col-TF-1 targeting senescence cells, a monoclonal antibody mAb SC-1 matched with the ternary fusion polypeptide Col-TF-1, an anti-aging composition containing the ternary fusion polypeptide Col-TF-1 and the monoclonal antibody mAb SC-1, and application of the ternary fusion polypeptide Col-TF-1 The fusion polypeptide is formed by connecting a targeting peptide for targeting a senescence cell surface uPAR receptor, a collagen active peptide for promoting collagen synthesis and an immunomodulatory peptide for activating NK cells in series through a flexible linker GGGGS, and the amino acid sequence is as shown in SEQ ID NO.1. The invention further discloses a preparation method of the fusion polypeptide. Through CDR region humanized reconstruction and pH sensitive histidine switch design, the affinity of the matched antibody mAb SC-1 is improved by 5 times in a subacid environment, and the ADCC effect is enhanced through fucose-deficient host cells. Experiments show that when the fusion polypeptide is combined with the antibody, the senescent cell clearance rate can reach 45.2%, the collagen density is increased by 83.5%, and the effect is obviously superior to that of a single drug. The composition provided by the invention can be applied to the fields of cosmetics, medical instruments, medicines and functional foods, and provides a new strategy for treatment of senescence-related diseases and development of anti-senescence products.

The invention relates to the technical field of biology, and discloses a method and equipment for dynamically detecting damage caused by ROS, and the method comprises the following steps: A, mixing ROS with a DNA skeleton nanostructure, and carrying out oxidative damage reaction; step B, within a period of time after the oxidative damage reaction occurs, sampling the morphological characteristics of the reaction product at multiple time points, and observing the change process of the morphological characteristics; c, according to the change process, the degree of damage caused by ROS to the DNA skeleton nanostructure is judged, and equipment capable of achieving the method comprises an ROS generation module, the DNA skeleton nanostructure, an oxidative damage reaction module and a data analysis module. The method can solve the problem that two types of ROS are difficult to visually distinguish in the prior art, can be used as a general system for evaluating the ROS regulation effect and performance of a nano material, and provides a new insight and method for deeply understanding the effect of ROS in biology and medicine, especially prevention and treatment of cancer and senescence related diseases.

The technology relates in part to compositions containing a cell penetrating peptide that can be used to selectively reduce a senescent cell population. The technology also relates to methods of treatment of ageing and ageing-associated diseases using a cell penetrating peptide to selectively reduce a senescent cell population.

The application discloses application of a novel peptide UHP in preparation of a medicine for treating and / or preventing delayed aging, and belongs to the technical field of biological medicines.The novel peptide UHP is composed of 37 L-type amino acids including a transmembrane peptide HIV-TAT.It is proved by cell experiments that the novel peptide UHP significantly improves the aging phenotype of a HGPS cell model simulated by overexpression of progerin and a replicative senescent human normal fibroblast cell, reduces the SA-beta-gal positive cell proportion and the expression of SASP factors, and increases the expression levels of cell proliferation markers Ki67, Lamin B1 and Cyclin A2.It is proved by animal experiments that the novel peptide UHP can improve the progeria phenotype, body weight and exercise capacity of a progeria mouse, relieve fibrosis in multiple tissues, improve the skin aging phenotype, and prolong the survival period of the progeria mouse, thereby providing a new medicine selection for clinical treatment of aging-related diseases.

The invention discloses an application of N4-acetylcytidine (ac4C) in preparation of a medicine for delaying senescence and prolonging life. The method is realized by reducing the overall ac4C modification level of RNA (including rRNA, tRNA, mRNA, ncRNA and the like) in a living body, and specifically can be realized by inhibiting the expression of a key catalytic adapter protein THUMPD1 or using an inhibitor targeting THUMPD1 / ac4C. The invention also provides an application of a reagent for detecting the aging degree or diagnosing aging-related diseases, such as Alzheimer's disease, mitochondrial diseases, tumors and the like, in preparation of a detection kit based on the ac4C modification level of a specific target RNA molecule, and provides a brand new target spot and strategy for aging intervention and accompanying disease diagnosis and treatment.

The present invention provides novel 2,4-dinitrophenol (DNP) derivatives and prodrugs thereof as modulators of mitochondrial function. The present invention also provides pharmaceutical compositions comprising the compounds of the present invention and methods for using the same to treat various diseases and conditions associated with or related to mitochondrial dysfunction (e.g., obesity, diabetes, insulin resistance, liver disease, heart or kidney failure, neurodegenerative diseases, and aging-related diseases, including but not limited to sarcopenia, osteoporosis, etc.).

The present invention provides an miR 1978 inhibitor and use thereof in treating a senescence-related disease. The etiology of senescence-related diseases is proposed, and the overexpression of miR 1978 derived from the mitochondrial genome in cell line SHSY5Y is proven to give rise to decreased mRNA expression and protein levels of DHFR, KIF5C, and MSH3; as a result, SHSY5Y cell division is arrested in the G1 phase of the cell cycle, the number of cells in the G2 / M phase is significantly reduced, and meanwhile, the number of apoptotic cells is increased. Compared with a control, cells containing miR1978 have different nuclear DNA methylation states. A plurality of Alzheimer's disease-related proteins, such as APP, Tau, p-Tau, and APOE, or Parkinson's disease-related proteins, such as α-synuclein, are increased in the SHSY5Y cell line containing miR 1978, etc.

The invention discloses application of a targeted stimulating molecule in preparation of drugs, health care products and cosmetics for preventing and treating natural aging, and relates to the field of biological medicines. The molecule provided by the invention can mediate the interaction between senescence cells and immune cells, enhance the endogenous immune function, and achieve the purposes of effectively removing senescence cells and improving senescence-related diseases. One end of the functional molecule for targeted senescence cell immune sensitization targets senescence cell membrane molecules, glutamic acid is marked on the surfaces of senescence cells, coupling between endogenous immune cells and the senescence cells is mediated, and adhesion and removal of the senescence cells by the immune cells are promoted. The molecule can regulate the immune microenvironment of senescent tissues, effectively reduce the number of positive senescent cells of senescence-related beta-galactosidase, improve the natural senescence phenotype of an organism and recover the phenotype and function of senescent skin.

The present invention relates to a composition for preventing, alleviating, or treating neuronal aging-related diseases or disorders, the composition comprising extracellular vesicles derived from three-dimensional spheroid-type cell aggregates. The extracellular vesicles according to the present invention can reduce the expression of aging-related proteins and induce reactivation of aged neural stem cells, and thus can be used to treat various neuronal aging-related diseases or disorders by preventing, alleviating, or treating the aging of neurons.

The invention discloses an application of a substance taking Angpt18 as a target in preparation of a medicine for treating and delaying senescence, and the key regulation effect of an Angpt18 gene in the occurrence and progression process of normal senescence and senescence-related diseases is found for the first time through systematic and in-depth research; further experiments prove that by inhibiting or down-regulating the expression of the Angpt18 gene, the senescence process can be obviously delayed, and the expressions such as hypomnesia and behavioral ability decline in the senescence process can be effectively improved. Therefore, the Angpt18 gene can be used as an important intervention target for senescence and related diseases thereof, can be used for developing drugs with senescence delaying or treatment effects, can also be used as a biomarker for evaluating the senescence degree and diagnosing and prognosing the related diseases of senescence, and has wide application prospects and clinical transformation values.

The application discloses an engineered exosome targeting human urokinase-type plasminogen activator receptor uPAR and a preparation method and application thereof. Firstly, a high-affinity anti-human uPAR single-domain antibody VHH is prepared; then, a human umbilical cord mesenchymal stem cell engineering cell line expressing a VHH-PTGFRN fusion protein is constructed, and the engineered exosome is prepared and purified by combining three-dimensional hypoxic culture, chemical induction and size-exclusion chromatography technology. The engineered exosome comprises four comparative samples, wherein the core sample Exo^(VHH / miR) can simultaneously display the anti-uPAR VHH on the membrane surface to realize targeted delivery and enrich miR-193b-3p in the chamber to realize gene silencing, and the synergistic effect of the two can efficiently remove the uPAR high-expression senescent cells and inhibit the senescence-associated secretory phenotype SASP. The engineered exosome has the advantages of standardized preparation process, high yield and high purity, strong targeting, excellent curative effect and good safety, and can be used for preparing a treatment preparation for anti-aging and aging-related diseases, and has important clinical application value.

This invention provides a method for preparing and applying a nanosystem for regulating the osteogenic microenvironment. The nanosystem comprises catalase, lactate oxidase, and a strontium-containing mineralized nanolayer. Experiments demonstrate that this nanosystem can effectively treat bone aging-related diseases, and that catalase and lactate oxidase have a synergistic effect. This invention provides a novel treatment strategy for bone aging-related diseases and has broad prospects for clinical translation.

The present invention belongs to the field of biomedical technology, and specifically relates to siRNA that targets and inhibits the expression of the demethylase ALKB-1 gene or ALKBH1 gene and its application. The present invention uses Caenorhabditis elegans as a model, designs and synthesizes highly specific targeted siRNA for ALKB-1, and delivers it into the nematode body to achieve specific knockdown of ALKB-1, significantly delaying the aging process of Caenorhabditis elegans, and also has an improvement effect on aging-related diseases including Parkinson's. Through mechanism analysis, it was found that the anti-aging effect of specific siRNA targeted intervention of ALKB-1 is achieved by regulating the methylation modification of tRNA to affect protein homeostasis. The present invention provides a new reference method for the development of anti-aging drugs and gene therapy strategies based on siRNA targeted knockdown technology to intervene in the function of ALKB-1.

A method of treating an aging-related disorder includes identifying a subject having an aging-related disorder and administering to the subject a therapeutically effective amount of a desialylated O-glycosylated glycoprotein, wherein the therapeutically effective amount is between 0.1 mg / kg and 500 mg / kg with respect to a body weight of the subject. Also disclosed are methods for producing the desialylated O-glycosylated glycoprotein using a clonal cell lacking sialyltransferase activity.

Provided herein are pharmaceutical compositions and dietary supplements comprising vanadyl sulfate (VS) and method of use thereof for the induction of cell death in senescent cells. In particular. VS compositions find use in clearance of age-related and / or therapy-induced senescent cells and reduction / elimination of senescence associated secretory phenotype (SASP)-induced inflammatory environments in subjects. and therefore in the treatment / prevention of age-related conditions and / or cancer.

The invention relates to a construction method and application of a rapid aging animal model. According to the invention, the C5a protein is injected into the hippocampus of an animal in a brain stereotactic manner, so that the rapid aging animal model is successfully constructed. The rapid aging animal model construction method provided by the invention has high repeatability, and the rapid aging animal model can be efficiently and stably prepared; moreover, the rapid aging animal model constructed according to the method disclosed by the invention shows obvious and stable learning and memory disorder and aging-related phenotypes, including reduction of learning and memory ability, increase of aging marker level, damage of synapse-related protein and the like, has high representativeness, and can be applied to the rapid aging animal model. Therefore, the method is not only suitable for pathological mechanism research of senescence and related diseases or symptoms, but also provides a powerful tool for drug development of senescence related diseases or symptoms (such as cognitive hypofunction caused by senescence), and shows a good industrial application prospect.

The invention relates to the field of biological detection, in particular to a multi-omics combined screening cell senescence marker detection method and application thereof. According to the method, data of genomics, transcriptomics, proteomics and metabonomics are combined, and multi-dimensional data in the cell senescence process are subjected to high-throughput screening and integration by means of whole genome sequencing, RNA-Seq, a liquid chromatography-mass spectrometry technology and a gas chromatography-mass spectrometry technology. And adopting machine learning algorithms such as random forest, a support vector machine and deep learning to screen out key markers related to aging. The markers comprise genes, proteins and metabolites, and have relatively high sensitivity and specificity. Verification of different aging models proves that the screened markers change significantly in the aging process and can effectively reflect the biological characteristics of cell aging. The method provides new technical support and theoretical basis for research of an aging mechanism, early diagnosis of aging-related diseases and anti-aging treatment.

Provided herein are proteins comprising an anti-CD26 antigen-binding domain. Also provided herein are methods of treating an aging-related disease or an inflammatory disease in a subject that include administering to the subject one of these proteins or a cell expressing one of these proteins.

The invention belongs to the technical field of physiological detection, and provides a physiological age detection method and device based on the VOC concentration of gas exhaled by a human body, and the device comprises an exhaled gas sampler 6 and a data analysis processing device 7; the exhaled gas sampler 6 is used for collecting exhaled gas of a human body; the data analysis processing device 7 comprises a VOC detection sensor 9, a data processing module and a result output module; the VOC detection sensor 9 is used for detecting various target VOC concentrations in gas exhaled by a human body, and the data processing module is used for calculating the physiological age according to the various target VOC concentrations; the result output module is used for outputting the physiological age; through a non-invasive sample collection mode, the method is suitable for all people with physiological age detection requirements, covers the whole age group, reduces the sampling and detection cost, shortens the detection period, improves the prediction accuracy and stability, and finally realizes large-scale popularization and application of physiological age prediction. And support is provided for health management of the whole people and early warning of senescence-related diseases.

The invention discloses an application of a substance for reducing the activity and / or expression quantity of RPL22 protein in delaying senescence. Experiments prove that the senescence phenotype of cells can be delayed by deletion of the RPL22 protein, the senescence phenotype of the cells can be accelerated by overexpression of the RPL22 protein, in addition, in the senescence occurrence process or under the condition of overexpression of the RPL22 protein, the senescence phenotype of the cells can be accelerated by inducing reduction of the levels of HP1gamma, KAP1 and H3K9me3 heterochromatin proteins on a heterochromatin region on nucleolus rDNA, so that the senescence phenotype of the cells can be delayed, and the senescence phenotype of the cells can be accelerated. Then heterochromatin is induced to be depolymerized, the transcription level of rDNA is increased, rRNA expression is increased, and the nucleolus structure is affected. The deficiency of RPL22 can relieve the occurrence of the phenotypes. Therefore, the RPL22 can be used as a potential target for preventing, relieving or treating aging or aging-related diseases. The method has an important application value.

The present invention relates to a method for identifying the aging degree of a subject or a tissue or organ thereof, and for evaluating the effect of anti-aging interventions. Specifically, provided is a method for identifying the aging degree of a subject or a cell, tissue or organ thereof, or for evaluating the biological age of the subject or diagnosing premature aging disorders, which method predicts the aging status of a tissue or organ of a subject on the basis of the levels of DNA methylation, gene transcripts, proteins or metabolites. The present invention further relates to the use of metformin in the preparation of a drug for treating, preventing or delaying aging-related diseases or conditions in primates, preferably humans.

The invention provides application of a targeted histone H4K77 acetylation modified substance in preparation of a medicine for delaying immune aging, a modified stem progenitor cell and application of the modified stem progenitor cell, and belongs to the technical field of medicine. The target histone H4K77 acetylation modification or acetylation-like modification substance is a substance for increasing the histone H4K77 acetylation modification level or acetylation-like modification level in hematopoietic stem cells and / or hematopoietic progenitor cells. It is found for the first time that by increasing histone H4K77 acetylation modification or acetylation-like modification, immune senescence and systemic senescence caused by immune senescence can be effectively delayed, and immune senescence and systemic senescence related diseases caused by immune senescence can be treated. The invention provides a new choice for clinically delaying immune senescence and systemic senescence caused by immune senescence and treating immune senescence and systemic senescence related diseases caused by immune senescence, and has a wide application prospect.

The invention discloses a data processing device and system for detecting the aging degree and application of the data processing device and system. The technical problem to be solved is to detect the aging degree of an organism to be tested or cells to be tested. Specifically disclosed is a device, the device comprising: M1, a migration body condition acquisition module for acquiring the migration body condition of a subject body or a subject cell, the migration body condition comprising the number of migration bodies or the content of the migration bodies; the result output module is used for comparing the condition of the migration body of the tested organism or the tested cell with a reference value and giving a result, and the result comprises at least one of the following: C1, the aging degree of the organism or the cell; c2, physiological age of the organism or the cell, C3, whether the organism or the cell suffers from the senescence-related disease or not or the risk of the senescence-related disease, and C4, the senescence and / or age-related disease early-warning result can be judged through the device, and the senescence degree of the tested organism or the tested cell can be judged through the device.

According to the WHO, the population aged 60 and over will have doubled by 2050. Unfortunately, aging comes along with an explosion of aging-associated disorders, such as metabolic and cardiovascular diseases, bone and muscle weakening, cognitive dysfunction, that all contribute to the loss of functional capacities, leading to frailty and dependence. Now, the inventors reveal a premature aging phenotype, associating metabolic defects and muscle weakness, in a mouse model of Noonan Syndrome. Both clinical traits are linked to myeloid cells dysfunction and increased senescence, highlighting the role of SHP2 hyperactivation in the onset of aging-associated diseases. Thus the present invention relates to the use of SHP2 inhibitors for inhibiting senescence.

The present application relates to a biological age evaluation system based on clinical indicators, a construction method and application, belonging to the field of biological aging research. First, the clinical indicators of the subjects are collected, the estimation model of biological age is constructed based on the clinical indicators, and the biological aging rate is further calculated. The present application can be used to identify individuals with accelerated aging or delayed aging, realize the risk prediction of death and aging-related diseases and the risk stratification of the population. The present application considers the nonlinear relationship between clinical indicators and aging degree, so that the biological age estimated by the present method has better prediction effect on the risk of death and new onset of aging-related diseases. The present application quantifies biological age and biological aging rate based on clinical indicators, and the measurement of clinical indicators can be completed by routine physical examination and blood sampling once, which has the advantages of low cost and convenience, and can evaluate the biological aging rate in time after physical examination, and provide health guidance for individuals with accelerated aging.

The invention relates to certain chromanol, quinone or hydroquinone compounds and derivatives thereof for treatment or prophylaxis of aging, or idiopathic ageing-associated disorders such as vascular ageing or reduced renal function. Specifically, the present invention relates to chromanol compounds chosen from 6-hydroxy-2,5,7,8-5 tetramethylchroman-2-yl)(piperazin-1-yl)methanone (SUL-121), ((S)-6-hydroxy-2,5,7,8-tetramethyl-N-((R)-piperidin-3-yl)chroman-2-carboxamide hydrochloride (SUL-13), 6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)(4-(2-hydroxyethyl)piperazin-1-yl)methanone (SUL-109), or its enantiomers and pharmaceutically acceptable salts thereof.

The present disclosure provides pyrimidine nucleoside compounds, including torcitabine, thymidine, deoxyuridine, deoxycytidine and uridine, and methods to treat telomere biology disorders (TBDs) and aging-related diseases, including hematological disorder, liver disease, or hepatic fibrosis, comprising administering to a subject diagnosed with said telomere biology disorder a therapeutically effective amount of said compounds.

The present invention relates to the field of biomedicine. Disclosed are a molecule for targeting senescent cells to stimulate endogenous immunity and use thereof. The drug provided by the present invention can mediate the interaction between senescent cells and immune cells, enhance the endogenous immune function, and achieve the goals of effectively clearing senescent cells and ameliorating aging-related diseases. A class of functional molecules targeting immune sensitization of senescent cells is provided. One end of the molecule targets membrane molecules of senescent cells, and labels the surface of senescent cells with glutamic acid, so as to mediate "coupling" between endogenous immune cells and senescent cells, thereby promoting the adhesion and clearance of senescent cells by immune cells. The molecule can regulate the immune microenvironment of aging tissues, and effectively reduce the number of senescence-associated β-galactosidase-positive senescent cells, while reversing fibrosis and improving the natural aging phenotype.

Methods and compositions are provided for treating aging-related diseases and disorders associated with protein misfolding, protein aggregation, or endoplasmic reticulum stress by administering zinc transporter protein 7 (ZIP7) or ZIP7 in combination with regulatory particle non-ATPase 11 (Rpn11). Methods of gene therapy are also provided for expressing ZIP7 and Rpn11 in vivo in effective amounts sufficient to treat an aging-related disease or disorder associated with protein misfolding, protein aggregation, or endoplasmic reticulum stress.